Walley Critical Care (2016) 20:270 DOI 10.1186/s13054-016-1439-6 REVIEW Open Access Left ventricular function: time-varying elastance and left ventricular aortic coupling Keith R. Walley Abstract heart must have special characteristics that allow it to respond appropriately and deliver necessary blood flow Many aspects of left ventricular function are explained and oxygen, even though flow is regulated from outside by considering ventricular pressure–volume characteristics. the heart. Contractility is best measured by the slope, Emax, of the To understand these special cardiac characteristics we end-systolic pressure–volume relationship. Ventricular start with ventricular function curves and show how systole is usefully characterized by a time-varying these curves are generated by underlying ventricular elastance (ΔP/ΔV). An extended area, the pressure– pressure–volume characteristics. Understanding ventricu- volume area, subtended by the ventricular pressure– lar function from a pressure–volume perspective leads to volume loop (useful mechanical work) and the ESPVR consideration of concepts such as time-varying ventricular (energy expended without mechanical work), is linearly elastance and the connection between the work of the related to myocardial oxygen consumption per beat. heart during a cardiac cycle and myocardial oxygen con- For energetically efficient systolic ejection ventricular sumption. Connection of the heart to the arterial circula- elastance should be, and is, matched to aortic elastance. tion is then considered. Diastole and the connection of Without matching, the fraction of energy expended the heart to the venous circulation is considered in an ab- without mechanical work increases and energy is lost breviated form as these relationships, which define how during ejection across the aortic valve. Ventricular cardiac output is regulated, stretch the scope of this re- function curves, derived from ventricular pressure– view. Finally, the clinical relevance of this understanding volume characteristics, interact with venous return is highlighted by considering, for example, why afterload curves to regulate cardiac output. Thus, consideration of reduction is an excellent therapy for systolic heart failure ventricular pressure–volume relationships highlight but fails to help, and instead harms, when systolic heart features that allow the heart to efficiently respond to failure is not the problem. any demand for cardiac output and oxygen delivery. Ventricular function curves Background Classic ventricular function curves The heart is a muscle pump that delivers blood at a high Starling function curves, or ventricular function curves, pressure to drive passive blood flow through a complex relate the input of the heart to output (Fig. 1) [1]. Any arterial and venous circuit. The demand for blood flow input and any output can be considered. For the heart is determined by metabolic activity of the tissues. For ex- we most frequently use right atrial pressure (central ven- ample, increased skeletal muscle work leads to increased ous pressure) or left atrial pressure (pulmonary capillary demand for oxygen so blood flow must increase to this wedge pressure) as clinically measurable inputs to the specific muscle. Since the need for blood flow is deter- heart (preload). Cardiac output (blood flow out of the mined by peripheral tissue demands, it follows that heart in liters per minute) is a common measure of out- blood flow must be regulated by the periphery. So the put of the heart. Other inputs and outputs yield different but related ventricular function curves. As the preload of the heart increases, cardiac output Correspondence: [email protected] — ’ Centre for Heart Lung Innovation, St. Paul’s Hospital, University of British increases sometimes called Starling s law of the heart Columbia, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada or the Frank–Starling relationship [2]. This relationship © 2016 Walley. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Walley Critical Care (2016) 20:270 Page 2 of 11 stroke work is plotted against end-diastolic volume the Ventricular Function Curve relationship is highly linear and fairly insensitive to load- ing conditions. The slope of this relationship is a meas- ure of ventricular contractility [7]. These modified ventricular function curves are more specific for intrin- sic ventricular contractile function but fall short of perfect. Because of different strengths and weaknesses, different variants of ventricular pump function inputs and outputs can be chosen strategically to address specific questions. In a clinical context central venous pressure (right ventricular end-diastolic pressure) and cardiac output are readily measurable and are often most appropriate. Alternative approaches to measurement on intrinsic myocardial contractility included consideration of the Fig. 1 This classic ventricular function curve relates input of the rate of change of ventricular chamber pressure during heart (end-diastolic pressure in mmHg) to output of the heart isovolumic systole—before “afterload” is seen by the (cardiac output in liters per minute). The ventricular function curve contracting ventricle. The maximum rate of change of shifts up and to the left when ventricular systolic contractility ventricular pressure, dP/dtmax, occurs late in isovolumic increases. However, increased diastolic compliance and decreased systole and increases when contractility is increased [8] afterload can also shift the ventricular function curve up and to the left (for example, by addition of adrenergic agents or cal- cium). While dP/dtmax avoids the problem of afterload effect, dP/dtmax is sensitive to changes in preload. Not is curvilinear (Fig. 1) so that, at high preload, further surprisingly, when isovolumic contraction starts at a increases in preload yield diminishing increases in greater end-diastolic volume (VED) then dP/dtmax is cardiac output. A specific ventricular function curve greater. Therefore, empirical corrections have been ap- applies to a specific ventricular contractile state, dia- plied. (dP/dtmax)/VED is another adjusted measure of stolic compliance, and afterload. Using cardiac output ventricular contractile function [9]. An interesting exten- as pump output, if ventricular contractility increases sion relates these isovolumic pressure measurements to (at a constant afterload), then the ventricular function sarcomere shortening. Vmax [6], the maximum rate of curve shifts up and to the left so that, at the same sarcomere shortening, was calculated by considering end-diastolic pressure (preload), a greater stroke vol- units of cardiac muscle (sarcomeres) to be made up of a ume and cardiac output is achieved [1] (Fig. 1, dashed contractile element and a linear series elastic ele- line). Improved ventricular diastolic compliance and ment—the series elastic element converting contractile decreased afterload (aortic pressure) also results in in- element shortening into pressure. In analogy to cardiac creased stroke volume (at a constant contractile state) muscle velocity–length relationships [10], the maximum so these changes also shift the ventricular function velocity of shortening can be extrapolated from a plot of curve up. dP/dt (representing velocity of contractile element short- ening) versus ventricular pressure (representing con- Modified ventricular function curves tractile element length). This approach appeared to The motivation behind early studies of ventricular func- circumvent afterload sensitivity and incorporated pre- tion curves was the desire to identify intrinsic ventricu- load. However, these and related computed indices all lar contractile function. Classic Starling function curves remain sensitive to changes in preload, afterload, and shift down with increased afterload [3] without a change heart rate to varying degrees. in contractility of the heart [4]. Therefore, modifications “Curve-fitting” approaches to modifying ventricular to ventricular function curves were considered. In some function curves did not conceptually connect easily with versions “output” was changed to stroke work or stroke underlying mechanism—Hill’s sliding filament model of work per minute (stroke power) [5]. Stroke work incor- muscle contraction. While isovolumic phase measure- porates afterload since it is pressure afterload × stroke ments were linked to underlying mechanism, they re- volume. In some versions “input” was changed to end- quired many debatable assumptions. Consideration of diastolic volume [6]. This addressed the issue of non- ventricular pressure–volume relationships made the linear diastolic compliance [5]. Probably the zenith of connection to underlying mechanism and incorporated modifications to ventricular function curves is the the concepts of preload, afterload, diastolic compliance, concept of preload recruitable stroke work [7]. When and contractility [11]. Walley Critical Care (2016) 20:270 Page 3 of 11 Ventricular pressure–volume